Amino acid metabolism in primary bone sarcomas.
Primary bone sarcomas, including osteosarcoma (OS) and Ewing sarcoma (ES), are aggressive tumors with peak incidence in childhood and adolescence. The intense standard treatment for these patients consists of combined surgery and/or radiation and maximal doses of chemotherapy; a regimen that has not seen improvement in decades. Like other tumor types, ES and OS are characterized by dysregulated cellular metabolism and a rewiring of metabolic pathways to support the biosynthetic demands of malignant growth. Not only are cancer cells characterized by Warburg metabolism, or aerobic glycolysis, but emerging work has revealed a dependence on amino acid metabolism. Aside from incorporation into proteins, amino acids serve critical functions in redox balance, energy homeostasis, and epigenetic maintenance. In this review, we summarize current studies describing the amino acid metabolic requirements of primary bone sarcomas, focusing on OS and ES, and compare these dependencies in the normal bone and malignant tumor contexts. We also examine insights that can be gleaned from other cancers to better understand differential metabolic susceptibilities between primary and metastatic tumor microenvironments. Lastly, we discuss potential metabolic vulnerabilities that may be exploited therapeutically and provide better-targeted treatments to improve the current standard of care.


Role of delta-opioid receptor agonists on infarct size reduction in swine.
Opioids are involved in cardiac ischemic preconditioning. Important species differences in cellular signaling mechanisms, antiarrhythmic, and antistunning effects have been described. The role of the delta-opioid receptor activation in swine remains unknown. Forty minutes before a 45-min occlusion and 180-min reperfusion of the left anterior descending coronary artery, open-chest, pentobarbital-anesthetized swine received either 1) saline (controls); 2) [D-Ala(2),D-Leu(5)]enkephalin (DADLE); 3) [D-Pen(2,5)]enkephalin (DPDPE); 4) deltorphin-D, a novel delta(2)-opioid agonist; or 5) ischemic preconditioning (IP). Assessed were 1) infarct size to area at risk (IS, triphenyltetrazolium staining), 2) regional and global myocardial function (sonomicrometry, ventricular pressure catheters), and 3) arrhythmias (electrocardiogram analyses). It was found that DPDPE and deltorphin-D pretreatment reduced IS from 64.7 +/- 5 to 36.5 +/- 6% and 27.4 +/- 11% (P < 0.01), respectively, whereas DADLE had no effect (66.8 +/- 3%). Both IP and DADLE had a proarrhythmic effect (P < 0.01). However, no differences in global or regional myocardial function or arrhythmia scores were observed between groups. This suggests that delta-receptor-specific opioids provide cardioprotection in swine.


Iron Absorption in Celiac Disease and Nutraceutical Effect of 7-Hydroxymatairesinol. Mini-Review.
Anemia is the main extra-gastrointestinal symptom in inflammatory bowel diseases (IBDs). Interleukin-6 (IL-6) and other cytokines are secreted and act in the microenvironment of the small intestine mucous membrane of IBD patients. Iron is essential for multiple cell functions and its homeostasis is regulated by the hepcidin-ferroportin axis. Hepcidin (HEPC) is mainly produced by the liver in response to iron needs but is also an acute phase protein. During inflammation, hepcidin is upregulated by IL-6 and is responsible for iron compartmentalization within cells, in turn causing anemia of inflammation. Tissues other than liver can produce hepcidin in response to inflammatory stimuli, in order to decrease iron efflux at a local level, then acting in an autocrine-paracrine manner. In IBDs and, in particular, in celiac disease (CeD), IL-6 might trigger the expression, upregulation and secretion of hepcidin in the small intestine, reducing iron efflux and exacerbating defective iron absorption. 7-Hydroxymatairesinol (7-HMR) belongs to the family of lignans, polyphenolic compounds produced by plants, and has nutraceutical antioxidant, anti-inflammatory and estrogenic properties. In this mini-review we revise the role of inflammation in IBDs and in particular in CeD, focusing our attention on the close link among inflammation, anemia and iron metabolism. We also briefly describe the anti-inflammatory and estrogenic activity of 7-HMR contained in foods that are often consumed by CeD patients. Finally, considering that HEPC expression is regulated by iron needs, inflammation and estrogens, we explored the hypothesis that 7-HMR consumption could ameliorate anemia in CeD using Caco-2 cells as bowel model. Further studies are needed to verify the regulation pathway through which 7-HMR may interfere with the local production of HEPC in bowel.


Haematology patients and the risk of transfusion transmitted infection.
A 2014 study by NHS Blood and Transplant indicated that over one quarter of red cells were transfused to patients with haematological conditions. For platelet components, the figure is higher. Certain diagnostic groups, such as haemoglobinopathies, myelodysplastic syndromes and some haemato-oncology patients, receive multiple transfusion episodes, either over long periods, or more intensively over shorter periods. Haematology patients account for the majority of the multi-transfused population. The risk of transfusion-transmitted infection (TTI) increases with number of donor exposures, and the consequences of TTI are often more significant in immunosuppressed individuals. Historically, use of pooled plasma products in patients with clotting disorders resulted in widespread transmission of hepatitis B virus, hepatitis C virus and human immunodeficiency virus before effective screening and viral inactivation methods were introduced.


The role of manual rotation in avoiding and managing OVD.
Manual rotation (MR) is the most common technique used by accoucheurs who wish to correct malposition of the foetal head to either avoid or facilitate an operative vaginal delivery (OVD). MR can be performed using either a whole-hand or a digital approach. MR should be formally taught and trainees should be assessed for competence, and later, performance should ideally be tracked with statistical control charts. There is paucity of robust evidence evaluating MR relative to the other methods of rotational OVD: rotational forceps (RF) and rotational ventouse (RV). Furthermore, there is little evidence concerning long-term maternal outcomes of rotational OVD. A prospective randomised trial of MR versus either RF or RV is clearly needed, along with a core outcome set for OVD to facilitate comprehensive evaluation programmes that focus on aspects pertaining to women.


Urinary transforming growth factor beta1 levels in hepatitis C virus-related chronic liver disease: correlation between high levels and severity of disease.
To assess the clinical relevance of transforming growth factor beta1 (TGF-beta1) in chronic liver disease, urinary TGF-beta1 and circulating aminoterminal propeptides of type III procollagen (PIIINP) levels were determined by radioimmunoassay in 100 cirrhotic patients, 44 patients with chronic hepatitis, and 50 healthy controls. TGF-beta1 and PIIINP levels in cirrhotic patients were higher than those in patients with chronic hepatitis (each P < .0001) or healthy controls (each P < .0001), respectively. There was a correlation between TGF-beta1 and PIIINP levels in patients (r = .858, P < .0001). The higher the urinary TGF-beta1 level, the worse the severity of chronic liver disease (P < .001). TGF-beta1 levels in cirrhotic patients with antibodies to hepatitis C virus (anti-HCV) were higher than in those without (P < .0001). Compared with cirrhotic patients with hepatitis B surface antigen (HBsAg) alone, those with HBsAg and anti-HCV had higher TGF-beta1 levels (P < .001), a higher frequency of raised TGF-beta1 (P < .005), and a higher frequency of patients with Child-Pugh C (P < .005). Multivariate analysis indicated that the TGF-beta1 level was significantly correlated with the presence of cirrhosis. In conclusion, urinary TGF-beta1 levels may be used as a marker for hepatic fibrogenesis. Higher urinary TGF-beta1 levels correlate with more severe liver disease.


Intractable epilepsy in adults.
Drug-resistant or "intractable" epilepsy presents a major challenge for physicians, epilepsy associations and researchers. Dr. Leppik discusses the evaluation of patients who may be intractable, the nature of intractable epilepsy and the factors which contribute to intractability.


Sociodemographic determinants of maternal health service use in rural China: a cross-sectional study.
This study examined the relationship between sociodemographic characteristics and maternal health use from a policy perspective. It aimed to provide an overview of maternal health in Heilongjiang's rural provinces and its implications on rural areas in countries with low and middle income gross domestic products. This cross-sectional study used data from the Fifth Health Service Survey of Heilongjiang Province. Participants included 481 mothers who delivered a baby after August 15, 2008. Trained investigators collected data on their family and sociodemographic characteristics, antenatal care, delivery at specialised obstetric institutions (e.g. hospitals, clinics, other medical institutions), and postnatal care services. The number of women with more than five antenatal care visits and the delivery rate at specialised obstetric institutions were high. Approximately 50% of the participants had three or more postnatal care visits. Maternal healthcare use among women less than 20 years old and those with natural deliveries were higher. There were fewer antenatal care visits among women who had been pregnant once or twice before. Delivery rates at specialised obstetric institutions and the number of antenatal care visits were higher than the World Health Organization requirements, while the frequency of postnatal care visits were better than most countries. This study identified several demographic characteristics that influenced maternal health service use. Policymakers should consider these findings when developing maternal health policies that protect women's interests and expand free services. Additional resources should be given to increase the postnatal care capacity and quality of maternal healthcare.


Exploring a peptide nucleic acid-based antisense approach for CD5 targeting in chronic lymphocytic leukemia.
We herein report an innovative antisense approach based on Peptide Nucleic Acids (PNAs) to down-modulate CD5 expression levels in chronic lymphocytic leukemia (CLL). Using bioinformatics tools, we selected a 12-mer tract of the CD5 mRNA as the molecular target and synthesized the complementary and control PNA strands bearing a serine phosphate dipeptide tail to enhance their water solubility and bioavailability. The specific recognition of the 12-mer DNA strand, corresponding to the target mRNA sequence by the complementary PNA strand, was confirmed by non-denaturing polyacrylamide gel electrophoresis, thermal difference spectroscopy, circular dichroism (CD), and CD melting studies. Cytofluorimetric assays and real-time PCR analysis demonstrated the downregulation of CD5 expression due to incubation with the anti-CD5 PNA at RNA and protein levels in Jurkat cell line and peripheral blood mononuclear cells from B-CLL patients. Interestingly, we also observed that transfection with the anti-CD5 PNA increases apoptotic response induced by fludarabine in B-CLL cells. The herein reported results suggest that PNAs could represent a potential candidate for the development of antisense therapeutic agents in CLL.


Validation and application of a novel cholesterol efflux assay using immobilized liposomes as a substitute for cultured cells.
Estimation of the function as well as the amount of high-density lipoprotein (HDL) is required to predict the risk of cardiovascular disease development. Cholesterol efflux capacity (CEC) is the key metric for determining the antiatherosclerotic function of HDL. However, the assay methods currently used to calculate CEC are not ideal for clinical use as they require the culture of cells. In the present study, we developed a novel CEC assay using immobilized liposome-bound gel beads (ILGs), containing fluorescently labeled cholesterol, as a substitute for cultured cells. When apolipoprotein B-100 depleted serum, obtained by polyethylene glycol precipitation, was used as the cholesterol acceptors, the basic properties of this method, such as the available range of HDL-cholesterol, efflux temperature and time, and normalization parameters, indicate that this method is sufficient to estimate CEC. Furthermore, the CEC values obtained with this ILG method were also correlated with those obtained with a conventional method using THP-1 macrophages derived foam cells and 3H-cholesterol as a tracer (r = 0.932). Overall, this novel cholesterol efflux assay method is a realistic and effective alternative to current methods in the field while also being easier to use in clinical laboratories as neither cell culture, radioisotope nor ultracentrifugation is required.


Antidepressant Use After Aneurysmal Subarachnoid Hemorrhage: A Population-Based Case-Control Study.
To elucidate the predictors of antidepressant use after subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) in a population-based cohort with matched controls. The Kuopio sIA database includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland, with 3 matched controls for each patient. The use of all prescribed medicines has been fused from the Finnish national registry of prescribed medicines. In the present study, 2 or more purchases of antidepressant medication indicated antidepressant use. The risk factors of the antidepressant use were analyzed in 940 patients alive 12 months after sIA-SAH, and the classification tree analysis was used to create a predicting model for antidepressant use after sIA-SAH. The 940 12-month survivors of sIA-SAH had significantly more antidepressant use (odds ratio, 2.6; 95% confidence interval, 2.2-3.1) than their 2676 matched controls (29% versus 14%). Classification tree analysis, based on independent risk factors, was used for the best prediction model of antidepressant use after sIA-SAH. Modified Rankin Scale until 12 months was the most potent predictor, followed by condition (Hunt and Hess Scale) and age on admission for sIA-SAH. The sIA-SAH survivors use significantly more often antidepressants, indicative of depression, than their matched population controls. Even with a seemingly good recovery (modified Rankin Scale score, 0) at 12 months after sIA-SAH, there is a significant risk of depression requiring antidepressant medication.


Novel sensors of the regulatory switch on the regulatory light chain of smooth muscle Myosin.
Smooth muscle myosin can be switched on by phosphorylation of Ser-19 of the regulatory light chain. Our previous photocross-linking results suggested that an element of the structural mechanism for the regulatory switch was a phosphorylation-induced motion of the regulatory light chain N terminus (Wahlstrom, J. L., Randall, M. A., Jr., Lawson, J. D., Lyons, D. E., Siems, W. F., Crouch, G. J., Barr, R., Facemyer, K. C., and Cremo, C. R. (2003) J. Biol. Chem. 278, 5123-5131). Here we used three different approaches to test this notion, which are reactivity of cysteine thiols, pyrene and acrylodan spectral analysis, and pyrene fluorescence quenching. All methods detected significant differences between the unphosphorylated and phosphorylated regulatory light chain N termini in heavy meromyosin, a double-headed subfragment with an intact regulatory switch. These differences were not observed for subfragment-1, a single-headed, unregulated subfragment. In the presence of either ATP or ADP, phosphorylation increased the solvent exposure and decreased the polarity of the environment about position 23 of the regulatory light chain of heavy meromyosin. These phosphorylation-induced structural changes were not as evident in the absence of nucleotides. Nucleotide binding to unphosphorylated heavy meromyosin caused a decrease in exposure and an increase in polarity of the N terminus, whereas the effects of nucleotide on phosphorylated heavy meromyosin were the opposite. We showed a direct correlation between the kinetics of nucleotide binding/turnover and the conformational change reported by acrylodan at position 23 of the regulatory light chain. Acrylodan-A23C also reports the heads up (extended) to flexed (folded) transition in unphosphorylated heavy meromyosin. This is the first demonstration of direct coupling of nucleotide binding to conformational changes in the N terminus of the regulatory light chain.


Detecting mediastinal lymph node metastases in non-small-cell lung cancer using a combination of technetium-99m tetrofosmin chest single photon emission computed tomography and chest computed tomography.
The staging of non-small-cell lung cancer (NSCLC) to detect mediastinal lymph node (MLN) metastases is very important for determining the therapeutic strategy. Thirty-four patients with proven NSCLC were enrolled in this study. All patients underwent chest computed tomography (CT) and technetium-99m (Tc-99m) tetrofosmin chest single photon emission computed tomography (SPECT) preoperative staging. Mediastinal lymph node metastases were determined on the basis of postoperative pathologic findings to compare the diagnostic accuracy of chest CT with that of Tc-99m tetrofosmin chest SPECT. Tc-99m tetrofosmin chest SPECT showed a diagnostic accuracy rate of 85.3% in detecting MLN metastases. Chest CT had an accuracy rate of 73.5%. If either Tc-99m tetrofosmin chest SPECT or chest CT with positive findings was considered as positive findings, the sensitivity was 94.7%. If either Tc-99m tetrofosmin chest SPECT or chest CT with negative findings was considered as negative, the specificity was 93.3%. Tc-99m tetrofosmin chest SPECT was more accurate than chest CT in detecting MLN metastases in NSCLC patients. In addition, the combined use of Tc-99m tetrofosmin chest SPECT and chest CT could significantly increase the sensitivity and specificity compared with the single use of either Tc-99m tetrofosmin chest SPECT or chest CT.


CD8+CD122+ T cells, a newly identified regulatory T subset, negatively regulate Graves' hyperthyroidism in a murine model.
Graves' disease is a thyroid-specific autoimmune disease mediated by stimulatory autoantibodies against the TSH receptor (TSHR). We have previously shown in our mouse model with adenovirus expressing the TSHR that antibody mediated depletion of CD4(+)CD25(+) regulatory T cells (Tregs) enhances incidence and severity of hyperthyroidism in resistant and susceptible mouse strains, respectively. These data indicate that balance between effector T cells and Tregs is critical for disease development. This study was designed to evaluate the role played by another recently identified type of Treg, CD8(+)CD122(+) T cells, in our mouse model to delineate the significance of different types of Tregs in Graves' disease. Flow cytometry analysis showed that CD4(+)CD25(+) and CD8(+)CD122(+) T cells are distinct cell types, and anti-CD122 antibody effectively and selectively depleted CD8(+)CD122(+) T cells. As for CD4(+)CD25(+) Treg, CD8(+)CD122(+) T cell depletion increased the incidence of hyperthyroidism both in resistant and susceptible mice. Of interest, intrathyroidal lymphocytic infiltration was observed in some CD8(+)CD122(+) T cell-depleted, hyperthyroid resistant mice. These results indicate that in addition to CD4(+)CD25(+) T cells, CD8(+)CD122(+) T cells also play a crucial role in disease susceptibility in mouse Graves' disease. Thus, different types of Tregs appear to be involved in tolerance to a self-antigen, the TSHR.


Erythropoietin treatment of human ovarian cancer cells results in enhanced signaling and a paclitaxel-resistant phenotype.
Erythropoietin (Epo), a glycoprotein hormone that is the principal regulator of erythropoiesis, is known to act also on nonhematopoietic cell types. Epo receptors have been reported on several normal and neoplastic human cells and tissues, including ovarian cancer cells. We found that long-term Epo treatment of A2780 cells resulted in the development of a phenotype exhibiting both enhanced Epo signaling, evidenced by increased peak levels of phospho-Erk1/2 and increased paclitaxel resistance. This phenotypic effect was specific for paclitaxel, since no change in cisplatin or carboplatin sensitivity was observed. In addition, the change in phenotype was stable, even after the removal of Epo. Measurement of mono- and oligonucleosome formation revealed that long-term Epo treated A2780 cells exhibited markedly less apoptosis than nonerythropoietin treated cells at essentially all concentrations of paclitaxel tested. Western blot analyses revealed that the long-term Epo treated cells had significantly reduced expression of apoptosis-related proteins Bcl-2 and Bcl-10. These findings may have implications for the clinical use of recombinant human Epo and other erythropoiesis stimulating agents to correct anemia in paclitaxel-treated cancer patients.


The feasibility of achieving Elective Care Framework targets for total hip arthroplasty and total knee arthroplasty in Northern Ireland.
Waiting times for arthroplasty surgery in Northern Ireland are among the longest in the NHS, which have been further lengthened by the onset of the COVID-19 global pandemic in March 2020. The Department of Health in Northern Ireland has announced a new Elective Care Framework (ECF), with the framework proposing that by March 2026 no patient will wait more than 52 weeks for inpatient/day case treatment. We aimed to assess the feasibility of achieving this with reference to total hip arthroplasty (THA) and total knee arthroplasty (TKA). Mathematical modelling was undertaken to calculate when the ECF targets will be achieved for THA and TKA, as well as the time when waiting lists for THA and TKA will be cleared. The number of patients currently on the waiting list and percentage operating capacity relative to pre-COVID-19 capacity was used to determine future projections. As of May 2021, there were 3,757 patients awaiting primary THA and 4,469 patients awaiting primary TKA in Northern Ireland. Prior to April 2020, there were a mean 2,346 (2,085 to 2,610) patients per annum boarded for primary THA, a mean 2,514 (2,494 to 2,514) patients per annum boarded for primary TKA, and there were a mean 1,554 primary THAs and 1,518 primary TKAs performed per annum. The ECF targets for THA will only be achieved in 2030 if operating capacity is 200% of pre COVID-19 pandemic capacity and in 2042 if capacity is 170%. For TKA, the targets will be met in 2034 if capacity is 200% of pre-COVID-19 pandemic capacity. This modelling demonstrates that, in the absence of major funding and reorganization of elective orthopaedic care, the targets set out in the ECF will not be achieved with regard to THA and TKA. Waiting times for THA and TKA surgery in Northern Ireland are likely to remain greater than 52 weeks for most of this decade. Cite this article: Bone Jt Open 2022;3(4):302-306.


[ Nail calcium content in relation to age and bone mineral density].
The growth of nails, and their matrix components, are influenced by several physiological, pathological and environmental factors. Because of the slow rate of nail growth, the elemental composition of the nail is also expected to be affected by transient factors controlling serum components. The mineral components of nail clippings may therefore reflect the long-term patterns of mineral metabolism, such as the rise of creatinine concentration seen in nails in patients with renal failure with hypercreatinemia. Fingernail and toenail Ca concentrations decreased with age in both men and women, whereas Mg concentrations tended to increase. Postmenopausal women had lower finger nail Ca concentrations than premenopausal women. LBMD showed a significant positive correlation with finger nail Ca content. The measurement of finger nail Ca content may be useful as a predictor of osteoporosis.


Necrobiosis lipoidica.
We present a case of necrobiosis lipoidica (NL) of the right abdomen in a 75-year-old man. A skin biopsy performed showed a layered infiltrate of mono and multinucleated histiocytes palisaded around degenerated collagen bundles. Laboratory workup was unremarkable. The patient was treated with topical corticosteroids with cessation of progression of his disease, although the eruption did not resolve. There are a number of treatments for NL reported in the literature, all with varying efficacy. Although NL lesions are usually asymptomatic, patients with NL must be monitored closely for signs of ulceration or malignant transformation, in which case more aggressive treatment options may be warranted.


Increased peroxidase activity in Pendred's syndrome with hypothyroidism.
An 8-year-old boy with goiter and bilateral nerve deafness had a 46% discharge of radioiodine after thiocyanate administration. He was clinically euthyroid. Although the serum total T4 was low (2.4 mug/100 ml) and TSH was significantly high (181 muU/ml), the serum total T3 was normal (152 ng/100ml). It was considered that the increased release of TSH by the feedback mechanism in response to the low T4 resulted in a quite normal level of serum T3. The thyroid gland demonstrated a low stable iodine content, an increase in MIT/DIT ration and a decrease in iodothyronine. The thyroglobulin behaved normally in Sephadex G-200 chromatography and immunoreaction. Thyroid tissue exhibited increased peroxidase activity as measured by I3 formation. Increased peroxidase activity may be related to the observed increase in serum level of TSH.


Ethical principles of the American Psychological Association: an argument for philosophical and practical ranking.
Unlike the American Psychological Association (APA), the Canadian Psychological Association has adopted a code of ethics in which principles are organized in order of importance. The validity of this hierarchical organization has received some empirical and theoretical support. We conducted a theoretical analysis that revealed conceptual justification for a ranking of the 6 principles in the APA code. Such a ranking could assist psychologists in making more informed and consistent moral choices when confronted with ethical dilemmas that involve conflicts among principles.


Body size categorization in anorexia nervosa using a morphing instrument.
To test the feasibility of the technique of "morphing" for body image assessment purposes and to investigate whether females with anorexia nervosa (AN) categorize other female's body sizes similarly to controls. A morphing movie showing the transformation of a thin woman into an obese woman was presented. Females with AN and thin controls selected the sizes corresponding to the transitions between the body size categories thin, normal, fat, and obese. They were instructed to look at the woman in the movie as themselves (Self) versus someone else (Other). The AN group chose significantly lower transitions associated with the categories thin, normal, fat, and obese under the Self instruction than controls. Similarly, they selected lower settings for all but the obese category when looking at the body as someone else's. It was concluded that females with AN display a harsher judgment not only of their own body size and shape, but also of that of another woman, than women without an eating disorder. The morphing instrument was found to be sufficiently realistic, detailed, and sensitive for its intended purposes.


Automated optical field mapping using a single-mode fiber interferometer.
Spatial distribution of optical phase and amplitude can be measured by using a single-mode optical-fiber interferometric system. Following the first proposal of the measuring principle by the present authors in 1978, a further development of the measuring system is now reported. The major achievement is the use of a novel spatial filter and a set of photodetectors by which the interference fringe position is located. Combining them with analog signal-processing circuitry and with a mechanical feedback system, fully automated recording of the optical phase and amplitude distribution is successfully achieved. The method is used to measure phase-front distribution near a Gaussian beam waist.


Mini-MACS: development of the Manual Ability Classification System for children younger than 4 years of age with signs of cerebral palsy.
To develop the Mini-Manual Ability Classification System (Mini-MACS) and to evaluate the extent to which its ratings are valid and reliable when children younger than 4 years are rated by their parents and therapists. The Mini-MACS was created by making adjustments to the MACS. The development involved a pilot project, consensus discussions within an expert group, and the creation of a test version of the Mini-MACS that was evaluated for content validity and interrater reliability. A convenience sample of 61 children with signs of cerebral palsy aged 12 to 51 months (mean age 30.2mo [SD 10.1]) were classified by one parent and two occupational therapists across a total of 64 assessments. Agreement between the parents' and therapists' ratings was evaluated using the intraclass correlation coefficient (ICC) and the percentage of agreement. The first sentence of the five levels in the MACS was kept, but other descriptions within the Mini-MACS were adjusted to be more relevant for the younger age group. The ICC between parents and therapists was 0.90 (95% confidence interval [CI] 0.79-0.92), and for the two therapists it was 0.97 (95% CI 0.78-0.92). Most parents and therapists found the descriptions in the Mini-MACS suitable and easy to understand. The Mini-MACS seems applicable for children from 1 to 4 years of age.


Diagnostic validation of rapid molecular detection of Mycobacterium tuberculosis in pus samples by GeneXpert.
To evaluate the performance of GeneXpert for detection of mycobacterium tuberculosis in pus samples and compare its results with conventional techniques in terms of validity, rapidity and rifampicin resistance. This longitudinal, descriptive study was conducted at Jinnah Hospital, Lahore, Pakistan, from January 2012 to December 2015, and comprised pus samples of people suspected of having extra-pulmonary tuberculosis. Participants were included by using consecutive sampling technique. The pus samples were subjected to Ziehl-Neelsen smear microscopy and Lowenstein-Jensen culture as per World Health Organisation's protocol and GeneXpert as per manufacturer protocol. SPSS 17 was used for data analysis. Validity of GeneXpert and rifampicin resistance were determined and compared with Ziehl-Neelsen staining using Lowenstein-Jensen culture as the gold standard. Of the 212 pus samples, 84(39.6%) were positive on Lowenstein-Jensen culture with mean turnaround time of 20±6 days, 77(36.3%) on GeneXpert and 22(10.4%) on Ziehl-Neelsen smear. The highest detection rate of mycobacterium tuberculosis 62(80.5%) was in lymph node samples by GeneXpert. The sensitivity and specificity of GeneXpert were 91.6% and 100% respectively, while Ziehl-Neelsen smear showed a sensitivity26.2% and specificity of 100%. Rifampicin resistance was detected in 5(6.4%) pus samples by GeneXpert. GeneXpert had a higher validity compared to Ziehl-Neelsen smear microscopy.


Gut morphology and hepatic oxidative status of European sea bass (Dicentrarchus labrax) juveniles fed plant feedstuffs or fishmeal-based diets supplemented with short-chain fructo-oligosaccharides and xylo-oligosaccharides.
The effects of short-chain fructo-oligosaccharides (scFOS) and xylo-oligosaccharides (XOS) on gut morphology and hepatic oxidative status were studied in European sea bass juveniles weighing 60 g. Fish were fed diets including fishmeal (FM diets) or plant feedstuffs (PF diets; 30 FM:70 PF) as main protein sources (control diets). Four other diets were formulated similar to the control diets but including 1 % scFOS or 1 % XOS. At the end of the trial, fish fed PF-based diets presented histomorphological alterations in the distal intestine, whereas only transient alterations were observed in the pyloric caeca. Comparatively to fish fed FM-based diets, fish fed PF diets had higher liver lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activities, and lower glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase activities. In fish fed the PF diets, prebiotic supplementation decreased SOD activity and XOS supplementation further decreased CAT activity. In fish fed the FM diets, XOS supplementation promoted a reduction of all antioxidant enzyme activities. Overall, dietary XOS and scFOS supplementation had only minor effects on gut morphology or LPO levels. However, dietary XOS reduced antioxidant enzymatic activity in both PF and FM diets, which indicate a positive effect on reduction of hepatic reactive oxygen species production.


Parapharyngeal malignant ectomesenchymoma: combined malignant fibrous histiocytoma and primitive neuroectodermal tumour with neuroglial differentiation.
A parapharyngeal ectomesenchymoma consisting of mixed malignant fibrous histiocytoma and primitive neuroectodermal tumour with neuroglial differentiation occurred in a 36-year-old woman. Immunohistochemical and electron microscopic studies verified the combined mesenchymal and neuroectodermal components within the tumour. Only 9 similar cases, including the present one, are on record. The patients ranged in age from 6 months to 49 years, with an average age of 18 years. The male:female ratio was 4:5. The tumour location was widespread. All reported ectomesenchymomas were histopathologically malignant. Recurrence and/or metastasis was/were common. The neural crest has been suggested as the origin of the ectomesenchymomas.


[Current Status and Tasks of the Lung Medical Consultant System].
In order to overcome challenges of serious short supply of donor organs, a unique partnership between transplant consultant doctors and local physicians, named medical consultant( MC) system, started in 2002 to maximize the organ utilization rate. As the first step of this system, skillfull heart transplant surgeons were sent to procurement hospitals as MCs to assess donor organ function and provide intensive care to donors. Since 2006, the MC doctors have requested the donors' attending physicians to perform aggressive bronchial suctioning using bronchoscopy, leading to an improved lung utilization rate and better graft survival. Since 2011, more than 25 lung MCs have been registered to assess donor lungs and provide advices on intensive respiratory care to donors. The effects of this system on lung transplantation opportunities and outcomes were retrospectively reviewed in 187 brain-dead lung donor candidates, which were chronologically divided into 3 phases:Ⅰ( May 1998 to November 2006, n=44) and Ⅱ( December 2006 to January 2011, n=64), before and after MCs requested local attending physicians to perform aggressive bronchial suctioning using bronchoscopy, respectively;and phase Ⅲ (February 2011 to January 2013, n=79), after the emergence of lung MCs( Hoshikawa Y, et al. Transplant Proc 47( 3):746-750, 2015). The lung utilization rates in phases Ⅰ, Ⅱ, and Ⅲ, were 61, 72, and 75%( per donor);51, 65, and 68% (per lung, p=0.03). Graft death due to primary graft dysfunction was significantly more frequent in phase Ⅰ (13.3%) than in phases Ⅱ (3.6%) and Ⅲ (3.7%, per lung, p=0.04). The lung utilization rate of 63 brain-dead lung donor candidates for a period of one year from June 2020 to May 2021, which was analyzed anew for this article, was 83%( per donor) and 72%( per lung). We discussed current status and tasks of the lung MC system which has been operated for 10 years.


Isotopic Control over Self-Assembly in Supramolecular Gels.
It is common to switch between H2O and D2O when examining peptide-based systems, with the assumption being that there are no effects from this change. Here, we describe the effect of changing from H2O to D2O in a number of low-molecular-weight dipeptide-based gels. Gels are formed by decreasing the pH. In most cases, there is little difference in the structures formed at high pH, but this is not universally true. On lowering the pH, the kinetics of gelation are affected and, in some cases, the structures underpinning the gel network are different. Where there are differences in the self-assembled structures, the resulting gel properties are different. We, therefore, show that isotopic control over gel properties is possible.


Cell sheet technology for the regeneration of gastrointestinal tissue using a novel gastric perforation rat model.
Anastomotic leakage is a major postoperative complication. While cell sheet technology has been gaining popularity in the clinical field, the utility of cell sheets for containing contaminated enteral perforation remains unclear. We established a new gastric perforation rat model and evaluated the efficacy of the myoblast cell sheet to prevent leakage. To establish a suitable rat model, perforations of various sizes were made in the stomach. We then pasted the sheet onto the perforated stomach in our new model. After the operation, the rats were sacrificed and analyzed macroscopically and histologically. Serum levels of C-related protein and hyaluronic acid in the peritoneal cavity washing lavage were also evaluated. An incision 5 mm in length was found to be the most suitable for evaluation of the cell sheet performance. In the rats where the cell sheet had been pasted onto the perforation site, we noted less adhesion in the abdominal cavity and a significant reduction in the hyaluronic acid levels in the peritoneal cavity washing lavage. We evaluated the efficacy of cell sheets for preventing leakage of enteral contents in a gastric perforation rat model. Myoblast cell sheets were able to markedly reduce the degree of both intra-abdominal adhesion and inflammation.


cAMP stimulation of StAR expression and cholesterol metabolism is modulated by co-expression of labile suppressors of transcription and mRNA turnover.
The steroidogenic acute regulatory (StAR) protein is generated in rodents from 1.6 kb and 3.5 kb mRNA formed by alternative polyadenylation. The zinc finger protein, TIS11B (also Znf36L1), is elevated by cAMP in adrenal cells in parallel with StAR mRNA. TIS11b selectively destabilizes the 3.5 kb mRNA through AU-rich sequences at the end of the 3'UTR. siRNA suppression shows that TIS11b surprisingly increases StAR protein and cholesterol metabolism. StAR transcription is directly activated by PKA phosphorylation. cAMP responsive element binding (CREB) protein 1 phosphorylation is a key step leading to recruitment of the co-activator, CREB binding protein (CBP). A second protein, CREB regulated transcription coactivator (TORC/CRTC), enhances this recruitment, but is inhibited by salt inducible kinase (SIK). Basal StAR transcription is constrained through this phosphorylation of TORC. PKA provides an alternative stimulation by phosphorylating SIK, which prevents TORC inactivation. PKA stimulation of StAR nuclear transcripts substantially precedes TORC recruitment to the StAR promoter, which may, therefore, mediate a later step in mRNA production. Inhibition of SIK by staurosporine elevates StAR transcription and TORC recruitment to maximum levels, but without CREB phosphorylation. TORC suppression by SIK evidently limits basal StAR transcription. Staurosporine and cAMP stimulate synergistically. SIK targets the phosphatase, PP2a (activation), and Type 2 histone de-acetylases (inhibition), which may each contribute to suppression. Staurosporine stimulation through SIK inhibition is repeated in cAMP stimulation of many steroidogenic genes regulated by steroidogenic factor 1 (SF-1) and CREB. TIS11b and SIK may combine to attenuate StAR expression when hormonal stimuli decline.


Thyroid hormone-dependent differential regulation of multiple arginase genes during amphibian metamorphosis.
We have cloned three nonhepatic arginase genes in Xenopus laevis. The deduced amino acid sequences of the three arginases are almost identical and share about 60% identity with mammalian as well as Xenopus liver arginase. Both the liver and nonhepatic arginase genes are activated early during embryogenesis. The liver arginase gene is strongly expressed in tadpole liver, but weakly in other tissues. In contrast, the nonhepatic arginase genes have the strongest expression in the tadpole tail. During metamorphosis, the liver and nonhepatic arginase genes show distinct regulation patterns. In the intestine, both types of arginase genes are activated during the remodeling period. In the tail, the liver arginase gene is activated during tail resorption, whereas the nonhepatic ones are highly expressed throughout all stages examined. Finally, in the hindlimb, the liver arginase is up-regulated slightly during development, whereas the nonhepatic ones have low levels of expression until the end of metamorphosis. During 3,5,3'-L-triiodothyronine (T3)-induced metamorphosis, the nonhepatic arginase genes are activated very quickly, whereas the liver arginase gene is a late T3 response gene. These differential regulation patterns during normal and T3-induced metamorphosis suggest potential functions for the arginases during tissue remodeling.


Non equilibrium thermodynamics and the city: a new approach to urban studies.
A city can be conceived as a complex self-adaptive system. The multiple interactions among its structural elements and dynamic agents, its organization on multiple time-space scales, its exchanges with the external context, its irreversible dynamics, are signs of complexity. Some concepts from the evolutionary thermodynamics, such us the theory of dissipative structures, could be extended to the city in order to investigate its behaviour. This theoretical framework suggests to analyze the city in terms of entropy and negentropy production. An emergy analysis (spelled with an "m") of an urban region is presented in order to investigate how cities maintain their organization (and decrease their entropy) by virtue of constant energy inflows from the external environment. As a result, a non-homogeneous spatial pattern of emergy density is shown as an attempt to investigate the multiple relations and energy exchanges that take place in an urban region. This approach to urban studies introduces a new energy-based vision to understand cities.


Cytotoxicity of ether-linked phytanyl phospholipid analogs and related derivatives in human HL-60 leukemia cells and polymorphonuclear neutrophils.
A cytotoxic activity, highly selective for neoplastic cells, is expressed by 1-alkyl-2-methoxy-sn-glycero-3-phosphocholine and by other derivatives closely related to the chemical structure of platelet activating factor. The antineoplastic potencies of a new series of analogs tested in HL-60 human leukemia cells and human polymorphonuclear neutrophils are reported. The degree of cytotoxicity was documented according to the ability of each analog to 1) destroy leukemic or normal cells or 2) to release lactic acid dehydrogenase from these cells. An index of selectivity of the analogs for their cytotoxicity toward leukemia cells is presented. Substitution by the twenty carbon branched-chain phytanyl moiety in place of the straight chain alkyl ether-linked group at the sn-1 position of various phospholipid analogs resulted in a 3- to 10-fold reduction in their cytotoxic potency in HL-60 leukemia cells. The enantiomeric isomers (D-forms) of several of the analogs possessed slightly greater phospholipid analogs possessing the sn-2-acetyl (platelet activating factor) or sn-2- propionoyl substituents, both biologically active in their ability to aggregate platelets and to induce hypotension, were relatively innocuous in terms of the measured cytotoxic responses in both HL-60 cells and neutrophils.


Regulating the cytoprotective response in cancer cells using simultaneous inhibition of Hsp90 and Hsp70.
Both heat shock protein 90 and 70 (Hsp90, Hsp70) are cytoprotective proteins that regulate cell death by stabilizing and folding proteins. Taking a two-pronged approach, involving simultaneous inhibition of Hsp90 and Hsp70, leads to synergistic cell death, which makes this is an appealing clinical therapy.


Antimicrobial susceptibility and clonality of Streptococcus pneumoniae isolates recovered from invasive disease cases during a period with changes in pneumococcal childhood vaccination, Norway, 2004-2016.
Changes in pneumococcal antimicrobial resistance (AMR) have been reported following use of pneumococcal conjugate vaccines (PCVs) in childhood vaccination programmes. We describe AMR trends and clonality in Norway during 2004-2016; we studied 10,239 invasive pneumococcal disease (IPD) isolates in terms of serotypes, antimicrobial susceptibility, and for a systematically collected subset of 2473 isolates, multilocus sequence types (ST). The IPD cases were notified to the Norwegian Surveillance System for Communicable Diseases and pneumococcal isolates were collected through the National Reference Laboratory for Pneumococci. The cases are sourced from the entire Norwegian population. We supplemented the IPD isolates with isolates from carriage studies in children attending day-care, performed in 2006 (before mass childhood vaccination with PCV7), 2008 (2 years after PCV7 introduction), 2013 (2 years after the transition to PCV13), and 2015. IPD cases were 0-102 years old; median 64 years. Carriage study participants were typically aged 1-5 years. Overall, AMR was low; a maximum of 7% of IPD isolates were resistant, depending on the antimicrobial. Erythromycin and trimethoprim/sulfamethoxazole resistant IPD (ERY-R and SXT-R, respectively) decreased in the PCV7 period (2006-2010). In the PCV13 period (2011-2016) however, we saw an indication of increased non-susceptibility among IPD isolates. This increase was mainly due to non-vaccine serotypes 15A-ST63 (multidrug resistant), 24F-ST162 (SXT-R), 23B-ST2372 (penicillin non-susceptible and SXT-R) and 33F (ERY-R and clindamycin resistant). Resistant or non-susceptible IPD isolates were often clones introduced into Norway during the study period. The exception was ERY-R isolates; initially, these largely consisted of an established serotype 14-ST9 clone, which disappeared after introducing PCV7. The carriage study results mostly resembled the changes seen in IPD with a maximum of 9% of the participants per study carrying resistant pneumococci. As actual PCVs are not fully limiting AMR, higher-valency vaccines and prudent use of antimicrobials are still needed to temper pneumococcal AMR.


Work, health and disease among rural workers in wetlands: integrative review.
Rural workers represent the typical population of workers in the Brazilian Pantanal, their work environment being characterized by exuberant fauna and flora, but also countless hazards. The aim of the present study was to analyze work, health and disease aspects of rural workers in Pantanal and the corresponding risk factors. It consists in an integrative review of studies published from 2006 to 2016 located in databases Regional Library of Medicine (BIREME), Latin American and Caribbean Health Sciences Literature (LILACS), Scientific Electronic Library Online (SciELO), MEDLINE, PubMed, Periódicos Eletrônicos em Psicologia (PePSIC), the journal portal and dissertation database of the Brazilian Federal Agency of Support and Evaluation of Graduate Education (CAPES), dissertation databases of Universidade Estadual de Campinas, Universidade de São Paulo, Universidade Católica Dom Bosco (Campo Grande, Mato Grosso do Sul) and Universidade Federal do Mato Grosso do Sul, and Google Scholar. We retrieved 27 publications, being 18 scientific studies, 2 PhD and 5 MA dissertations and 2 e-books. Evidenced hazards include accidents involving animals, work overload, and exposure to weather conditions, viruses, bacteria and chemicals, among others. The results point to the need to implement actions considered in public policies for prevention, health promotion and recovery, with particular focus on safety and health at work.


High-Efficiency Nonfullerene Organic Solar Cells with a Parallel Tandem Configuration.
In this work, a highly efficient parallel connected tandem solar cell utilizing a nonfullerene acceptor is demonstrated. Guided by optical simulation, each of the active layer thicknesses of subcells are tuned to maximize its light trapping without spending intense effort to match photocurrent. Interestingly, a strong optical microcavity with dual oscillation centers is formed in a back subcell, which further enhances light absorption. The parallel tandem device shows an improved photon-to-electron response over the range between 450 and 800 nm, and a high short-circuit current density (J SC ) of 17.92 mA cm-2 . In addition, the subcells show high fill factors due to reduced recombination loss under diluted light intensity. These merits enable an overall power conversion efficiency (PCE) of >10% for this tandem cell, which represents a ≈15% enhancement compared to the optimal single-junction device. Further application of the designed parallel tandem configuration to more efficient single-junction cells enable a PCE of >11%, which is the highest efficiency among all parallel connected organic solar cells (OSCs). This work stresses the importance of employing a parallel tandem configuration for achieving efficient light harvesting in nonfullerene-based OSCs. It provides a useful strategy for exploring the ultimate performance of organic solar cells.


Megapixel multi-elemental imaging by Laser-Induced Breakdown Spectroscopy, a technology with considerable potential for paleoclimate studies.
Paleoclimate studies play a crucial role in understanding past and future climates and their environmental impacts. Current methodologies for performing highly sensitive elemental analysis at micrometre spatial resolutions are restricted to the use of complex and/or not easily applied techniques, such as synchrotron radiation X-ray fluorescence micro-analysis (μ-SRXRF), nano secondary ion mass spectrometry (nano-SIMS) or laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Moreover, the analysis of large samples (>few cm²) with any of these methods remains very challenging due to their relatively low acquisition speed (~1-10 Hz), and because they must be operated in vacuum or controlled atmosphere. In this work, we proposed an imaging methodology based on laser-induced breakdown spectroscopy, to perform fast multi-elemental scanning of large geological samples with high performance in terms of sensitivity (ppm-level), lateral resolution (up to 10 μm) and operating speed (100 Hz). This method was successfully applied to obtain the first megapixel images of large geological samples and yielded new information, not accessible using other techniques. These results open a new perspective into the use of laser spectroscopy in a variety of geochemical applications.


Nidogen-1 could play a role in diabetic kidney disease development in type 2 diabetes: a genome-wide association meta-analysis.
Diabetic kidney disease (DKD) affects about 40% of patients with diabetes. It is incurable and usually leads to end-stage renal disease (ESRD). The pathogenesis of DKD is still not fully understood, and the genetics of DKD have not yet been extensively studied. In this study, we investigate the genetic basis of DKD in type 2 diabetes (T2D) to provide more insights into the pathogenesis of the disease. Using the data provided by the UK Biobank (UKBB), we performed a DKD genome-wide association study (GWAS) in 13,123 individuals with T2D as well as two creatinine estimated glomerular filtration rate (eGFR) GWA studies: one in 26,786 individuals with T2D and the other in 339,080 non-diabetic individuals. We also conducted a DKD GWAS meta-analysis combining our results with those published by the surrogate markers for micro- and macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) consortium. We confirm two loci previously reported to be associated with chronic kidney disease (CKD) and eGFR in T2D. The UMOD-PDILT locus is associated with DKD (P = 1.17E-09) as well as creatinine eGFR in both people with T2D (P = 1.31E-15) and people without diabetes (P = 3.95E-73). The PRKAG2 locus is associated with creatinine eGFR in people with (P = 2.78E-10) and without (P = 5.65E-72) T2D. Our meta-analysis reveals a novel association between DKD and variant rs72763500 (chr1:236116561) which is a splicing quantitative trait locus (sQTL) for nidogen-1 (NID1) gene. Our data confirm two loci previously reported in association with CKD and creatinine eGFR in T2D. It also suggests that NID1, a major component of the renal tubular basement membrane, could play a role in DKD development in T2D. While our NID1 finding remains to be replicated, it is a step toward a more comprehensive understanding of DKD pathogenesis.


Ochratoxin A reduction in meat sausages using processing methods practiced in households.
The aim of this study was to investigate the possibilities of ochratoxin A (OTA) reduction in home-made meat products. Meat sausages (n = 50) produced from raw materials coming from pigs exposed to OTA-contaminated feed, were subject to common heat processes practiced in households (cooking, frying and baking). Concentrations of OTA in pre- and post-processed products were quantified using a validated immunoassay method, enzyme-linked immunosorbent assay, and confirmed using a high-performance liquid chromatography with fluorescence detection. In line with the differences in recipes used and the degree of OTA accumulation in raw materials, OTA concentrations established in Mediterranean and roast sausages were lower than those found in liver and blood sausages. Baking of contaminated sausages at the temperatures of 190-220°C (for 60 min) resulted in significant reduction of OTA levels (75.8%), while 30-min cooking (at 100°C) and frying (at 170°C) proved to be significantly less effective (e.g. yielding OTA reductions of 7.4% and 12.6%, respectively). The results pointed out that despite high OTA stability, heat processes are capable of reducing its concentration in home-made meat products, depending on the processing modality used.


[A case manifested overlapping neuropathologic features of both progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD)].
A 62-year-old man developed clumsiness, vertical ophthalmoplegia, right-side dominant parkinsonism, pyramidal signs, limb-kinetic apraxia and dementia. His brain MRI and SPECT revealed mild fronto-parietal atrophy and hypoperfusion predominately on the right side. At the age of 65, the patient died of sepsis. The duration of his illness was approximately 3 years. Clinical diagnosis was corticobasal degeneration (CBD). On neuropathological examination, there was no neuronal loss and many neurofibrillary tangles (NFTs) in the cerebral cortices. Basal ganglia and substantia nigra showed moderate to severe neuronal loss. And there were many NFTs and argyrophillic threads (threads) in the subthalamic nucleus and nuclei of the brainstem. These findings were almost compatible to those of PSP. However, the following findings were atypical for PSP, 1) mild atrophy and absence of gliosis in the tegmentum of the brain stem, 2) Mild neuronal loss in the subthalamic nucleus and the dentate nucleus without grumose degeneration. Furthermore, characteristic findings were noted on modified Gallyas-Braak stain. Numerous threads and many astrocytic plaques (AP) were shown in cerebral cortices, which were particular to CBD cases. So this case demonstrated neuropathological findings of both PSP and CBD. Therefore, it was difficult to classify this case as either PSP or CBD, and we diagnosed this case as a neuropathological overlapping case of both PSP and CBD.


A case of rare gastric metastasis of invasive lobular carcinoma of the breast.
Breast cancer is the most common type of cancer diagnosed among women worldwide. It significantly contributes to cancer-related mortality in females. Early-stage breast cancers have a high cure rate. However, distant metastasis of breast cancer due to haematological and lymphatic spread often leads to a poor prognosis. Gastric and duodenal metastasises are rarely observed in invasive lobular carcinoma of the breast. Early diagnosis is challenging due to the non-specific symptoms, the limited specificity of radiological investigations and the difficulty in obtaining adequate tissue biopsy. Herein, we report the clinical, radiological, and macroscopic features of a 72-year-old female with rare gastric metastasis of breast cancer and likely concurrent duodenal metastasis.


Self-reported work ability and work performance in workers with chronic nonspecific musculoskeletal pain.
To assess self-reported work ability and work performance of workers who stay at work despite chronic nonspecific musculoskeletal pain (CMP), and to explore which variables were associated with these outcomes. In a cross-sectional study we assessed work ability (Work Ability Index, single item scale 0-10) and work performance (Health and Work Performance Questionnaire, scale 0-10) among 119 workers who continued work while having CMP. Scores of work ability and work performance were categorized into excellent (10), good (9), moderate (8) and poor (0-7). Hierarchical multiple regression and logistic regression analysis was used to analyze the relation of socio-demographic, pain-related, personal- and work-related variables with work ability and work performance. Mean work ability and work performance were 7.1 and 7.7 (poor to moderate). Hierarchical multiple regression analysis revealed that higher work ability scores were associated with lower age, better general health perception, and higher pain self-efficacy beliefs (R(2) = 42 %). Higher work performance was associated with lower age, higher pain self-efficacy beliefs, lower physical work demand category and part-time work (R(2) = 37 %). Logistic regression analysis revealed that work ability ≥8 was significantly explained by age (OR = 0.90), general health perception (OR = 1.04) and pain self-efficacy (OR = 1.15). Work performance ≥8 was explained by pain self-efficacy (OR = 1.11). Many workers with CMP who stay at work report poor to moderate work ability and work performance. Our findings suggest that a subgroup of workers with CMP can stay at work with high work ability and performance, especially when they have high beliefs of pain self-efficacy. Our results further show that not the pain itself, but personal and work-related factors relate to work ability and work performance.


Experimental xenoimplantation of antlerogenic cells into mandibular bone lesions in rabbits: two-year follow-up.
Different types of cells require activation, and take part in annual, dynamic growth of deer antlers. Stem cells play the most important role in this process. This report shows the results of a two-year long observation of xenogenic implant of antlerogenic stem cells (cell line MIC-1). The cells were derived from growing antler of a deer (Cervus elaphus), seeded onto Spongostan and placed in postoperative lesions of mandibular bones of 15 experimental rabbits. The healing process observed in the implantation sites in all rabbits was normal, and no local inflammatory response was ever observed. Histological and immunohistochemical evaluations were performed after 1, 2, 6, 12 and 24 months, and confirmed the participation of xenogenic cells in the regeneration processes, as well as a lack of rejection of the implants. The deficiencies in the bones were replaced by newly formed, thick fibrous bone tissue that underwent mineralization and was later remodelled into lamellar bone. The results of the experiment with rabbits allow us to believe that antlerogenic cells could be used in reconstruction of bone tissues in other species as well.


Russujaponols A-F, illudoid sesquiterpenes from the fruiting body of Russula japonica.
Six new illudoid sesquiterpenes, russujaponols A-F (1-6), were isolated from the fruiting bodies of Russula japonica Hongo. Their structures were established primarily by 2D NMR experiments, and the structure of the main compound, russujaponol A (1), was confirmed by X-ray crystallographic analysis of its benzoate (1a). Russujaponol A (1) suppressed invasion of human fibrosarcoma (HT1080) cells into Matrigel in a concentration-dependent manner and caused 63% inhibition at 3.73 microM.


A method of increasing test range and accuracy of bioindicators: Geobacillus stearothermophilus spores.
Spores of Geobacillus stearothermophilus are very sensitive to changes in temperature. When validating sterilizing processes, the most common bioindicator (BI) is spores of Geobacillus stearothermophilus ATCC12980 and ATCC7953 with about 10(6) spores /BI and a D121-value of about 2 minutes in water. Because these spores of Geobacillus stearothermophilus do not survive at a F0-value above 12 minutes, it has not been possible to evaluate the agreement between the biological F-value (F(BIO)) and physical measurements (time and temperature) when the physical F0-value exceeds that limit. However, it has been proven that glycerin substantially increases the heat resistance of the spores, and it is possible to utilize that property when manufacturing BIs suitable to use in processes with longer sterilization time or high temperature (above 121 degrees C). By the method described, it is possible to make use of the sensitivity and durability of Geobacillus stearothermophilus' spores when glycerin has increased both test range and accuracy. Experience from years of development and validation work with the use of the highly sensitive glycerin-water-spore-suspension sensor (GWS-sensor) is reported. Validation of the steam sterilization process at high temperature has been possible with the use of GWS-sensors. It has also been shown that the spores in suspension keep their characteristics for a period of 19 months when stored cold (8 degrees C).


Irinotecan-induced bile acid malabsorption is associated with down-regulation of ileal Asbt (Slc10a2) in mice.
Irinotecan, (CPT-11), an antitumor agent primarily used for the treatment of solid tumors, has often compromised clinical application due to the inducement of severe delay-onset diarrhea. Bile acid malabsorption (BAM) is widely accepted as the common cause of diarrhea. However, whether CPT-11-induced diarrhea has correlation with BAM is unknown. The aim of this study was to investigate the effect of CPT-11 on the bile acid homeostasis in mice. The mice were administrated with CPT-11 intravenously for four consecutive days. The total bile acids (TBAs) levels in the small intestine, colon, feces, liver, serum and gallbladder were evaluated by automatic biochemical analyzer, and the individual bile acids were also measured by LC-MS/MS. Real-time qPCR and Western blot techniques were used to evaluate the mRNA and protein expressions of Cyp7a1, Cyp27a1, Asbt, Ostα/β. In situ loop method was carried out to evaluate the function of apical Na+-dependent bile salt transporter (Asbt). Results showed that the bile acid pool size was significantly reduced by 17%, 25%, and 40% respectively at 2, 3, and 4days post CPT-11 treatment. The fecal excretions of TBAs were significantly increased by 2.1-fold at 3 and 4days post CPT-11 treatment. The ileal expression of Asbt was significantly decreased at mRNA and protein levels, and the transport ability of Asbt was also attenuated after CPT-11 treatment. Moreover, the incidence of CPT-11-induced delay-onset diarrhea was also decreased after cholestyramine administration in CPT-11-treated mice. These results indicated that BAM may be partially responsible for CPT-11-induced delay-onset diarrhea, and the underlying mechanism may have correlation with down-regulation of the Asbt in the ileum of mice.


Pilot-Scale Melt Electrospinning of Polybutylene Succinate Fiber Mats for a Biobased and Biodegradable Face Mask.
The COVID-19 pandemic led to a huge demand for disposable facemasks. Billions were manufactured from nonbiodegradable petroleum-derived polymers, and many were discarded in the environment where they contributed to plastic pollution. There is an urgent need for biobased and biodegradable facemasks to avoid environmental harm during future disease outbreaks. Melt electrospinning is a promising alternative technique for the manufacturing of filter layers using sub-microfibers prepared from biobased raw materials such as polybutylene succinate (PBS). However, it is not yet possible to produce sub-micrometer PBS fibers or uniform nonwoven-like samples at the pilot scale, which hinders their investigation as filter layers. Further optimization of pilot-scale PBS melt electrospinning is therefore required. Here, we tested the effect of different parameters such as electric field strength, nozzle-to-collector distance and throughput on the final fiber diameter and sample uniformity during PBS melt electrospinning on a pilot-scale device. We also studied the effect of a climate chamber and an additional infrared heater on the solidification of PBS fibers and their final diameter and uniformity. In addition, a post-processing step, including a hot air stream of 90 °C for 30 s has been studied and successfully lead to a nonwoven-like structure including filaments that weld together without changing their structure. The finest fibers (1.7 µm in diameter) were produced at an applied electric field strength of -40 kV, a nozzle-to-collector distance of 5.5 cm, and a spin pump speed of 2 rpm. Three uniform nonwoven-like samples were tested as filter layers in a medical face mask by measuring their ability to prevent the transfer of bacteria, but the pore size was too large for effective retention. Our results provide insight into the process parameters influencing the suitability of melt-electrospun nonwoven-like samples as biobased and biodegradable filter materials and offer guidance for further process optimization.


Molecular characterization of thioredoxin-1 and thioredoxin reductase activity in mud crab Scylla paramamosain.
The thioredoxin (Trx) system consists of thioredoxin reductase (TrxR), Trx, and nicotinamide adenine dinucleotide phosphate (NADPH). TrxR is an NADPH-dependent oxidoreductase. Trx is a ubiquitous small protein with a redox-active disulfide bridge that plays important regulatory roles in some vital metabolic reactions. In this study, a cDNA sequence (SpTrx1) showing high identity to the first Trx gene was isolated from a hepatopancreas cDNA library of the mud crab Scylla paramamosain. The full-length cDNA of SpTrx1 consisted of 672 bp and contained a complete open reading frame of 318 bp encoding a polypeptide of 105 amino acids. Quantitative real-time polymerase chain reaction analysis revealed that SpTrx1 expression was ubiquitous in various organs of S. paramamosain, including the gill, muscle, heart, hemolymph, testis, and hepatopancreas. SpTrx1 expression was upregulated significantly after Vibrio parahaemolyticus challenge: it obviously rose at 48 h and reached the highest level at 72 h. Furthermore, TrxR activity was detected in the gill, heart, muscle, hemolymph, and hepatopancreas. The relative TrxR activity in different tissues after V. parahaemolyticus injection had the same tendency in each tissue (P < 0.01) as SpTrx1 expression. The TrxR activity increased 2 h after injection, peaked at 8 h, slowly decreased from 12 to 24 h, and returned to normal levels at 48 h. The consistency of the expression between the Trx transcript and TrxR activity demonstrated that Trx was closely related to TrxR in the Trx system in S. paramamosain, suggesting that it may participate in the immune system of mud crabs.


Delayed diagnosis of 22q11 deletion syndrome due to late onset hypocalcemia in a 11-year-old girl with imperforated anus.
Neonatal hypocalcemia and congenital heart defects has been known as the first clinical manifestation of the chromosome 22q11.2 deletion syndrome (22q11DS). However, because of its wide clinical spectrum, diagnosis of 22q11DS can be delayed in children without classic symptoms. We report the case of a girl with the history of imperforate anus but without neonatal hypocalcemia or major cardiac anomaly, who was diagnosed for 22q11DS at the age of 11 after the onset of overt hypocalcemia. She was born uneventfully from phenotypically normal Korean parents. Imperforate anus and partial cleft palate were found at birth, which were surgically repaired thereafter. There was no history of neonatal hypocalcemia, and karyotyping by GTG banding was normal. At the age of 11, hypocalcemia (serum calcium, 5.0 mg/dL) and decreased parathyroid hormone level (10.8 pg/mL) was noted when she visited our Emergency Department for fever and vomiting. The 22q11DS was suspected because of her mild mental retardation and velopharyngeal insufficiency, and a microdeletion on chromosome 22q11.2 was confirmed by fluorescence in situ hybridization. The 22q11DS should be considered in the differential diagnosis of hypocalcemia at any age because of its wide clinical spectrum.


Adaptive Evolution Favoring KLK4 Downregulation in East Asians.
The human kallikrein (KLK) cluster, located at chromosome 19q13.3-13.4, encodes 15 serine proteases, including neighboring genes (KLK3, KLK2, KLK4, and KLK5) with key roles in the cascades of semen liquefaction, tooth enamel maturation, and skin desquamation. KLK2 and KLK3 were previously identified as targets of adaptive evolution in primates through different mechanisms linked to reproductive biology and, in humans, genome-wide scans of positive selection captured, a yet unexplored, evidence for KLK neutrality departure in East Asians. We perform a detailed evaluation of KLK3-KLK5 variability in the 1000 Genomes samples from East Asia, Europe, and Africa, which was sustained by our own sequencing. In East Asians, we singled out a 70-kb region surrounding KLK4 that combined unusual low levels of diversity, high frequency variants with significant levels of population differentiation (FST > 0.5) and fairly homogenous haplotypes given the large local recombination rates. Among these variants, rs1654556_G, rs198968_T, and rs17800874_A stand out for their location on putative regulatory regions and predicted functional effects, namely the introduction of several microRNA binding sites and a repressor motif. Our functional assays carried out in different cellular models showed that rs198968_T and rs17800874_A operate synergistically to reduce KLK4 expression and could be further assisted by rs1654556_G. Considering the previous findings that KLK4 inactivation causes enamel malformations in humans and mice, and that this gene is coexpressed in epidermal layers along with several substrates involved in either cell adhesion or keratinocyte differentiation, we propose KLK4 as another target of selection in East Asians correlated to tooth and epidermal morphological traits.


[Simplified method of obtaining the correction factor for calculating ventricular volumes].
For the accurate measurement of ventricular volume it is required the obtainment of a correction factor for the magnification caused by the non-parallel X-rays and the "pincushion" distortion, which causes more magnification in the periphery than in the center of the fluoroscopic field. The Kasser and Kennedy method is based in the attainment of the relation between the actual and projected dimensions of a micrometrically calibrated grid filmed at the distance measured between the intensifier tube and the mid-thoracic line during the ventriculography. This technique is very accurate but expensive and troublesome. With the simpler catheter method it is obtained the relation between the projected and actual linear dimensions of the ventriculographic catheter inmediately before ventriculography. This study was aimed to compare the accuracy of the catheter method and two other proposed methods, in which the relation between the projected and actual dimensions were obtained by filming one central coin or five arranged through the fluoroscopic field at the distance measured between the tube and the patients during the ventriculography. These four correction factors were obtained in 15 patients undergoing a diagnostic cardiac catheterization. The catheter method showed a poor correlation with the grid method (r = 0.34), while both coin methods showed a high correlation with the grid method (r = 0.93 and 0.92, respectively). It is concluded that the catheter method is inaccurate and therefore is unwise to use it for the estimation of ventricular volumes. Because the peripheric distortion is clinically unimportant, the central coin methods is proposed as a simplified method for obtaining the magnification correction factor.(ABSTRACT TRUNCATED AT 250 WORDS)


Jellyfish anaphylaxis: A wide spectrum of sensitization routes.
Background: Recent studies demonstrated that, in the past few years, the number of jellyfish species is increasing worldwide; this increase can be explained by environmental and climatic reasons. Contacts with jellyfish can cause acute and chronic effects, including allergic reactions. Although anaphylaxis caused by jellyfish is a rare event, repetitive stings during bathing as well as marine sports and job activities represent important risk factors that can increase the probability of sensitization. Recently, it was also pointed out the possibility of anaphylaxis caused by jellyfish ingestion. In these cases, the sensitization could also be related to previous stings. In cases in which there is no history of jellyfish contact or ingestion, it has been hypothesized that there is a sensitization to an unknown cross-reactive antigen. Objective: The purpose of this work was to collect and review published studies and cases of anaphylaxis associated with jellyfish. Methods: We performed a medical literature data base search, which included English language articles published until September 2019, by using the key words "jellyfish" associated with "anaphylaxis" or "anaphylactic shock." Results: The results of our research showed that dangerous reactions can be caused both by contact and ingestion. Moreover, the latest changes in food habits, life style, and globalization could lead to a more frequent exposure to jellyfish both by contact and ingestion, and, consequently, to a higher probability of sensitization. Conclusion: Prospective studies and well-structured research are needed to better understand all the potential immunologic elements of jellyfish, to clarify its role in sensitization, and to avoid possible dangerous allergic reactions caused by cross-reactivity.


Risk factors and consequences of anastomotic leakage after Ivor Lewis oesophagectomy†.
Oesophageal carcinoma (EC) remains an aggressive disease. Despite extensive changes in therapeutic modalities, surgical resection remains the first choice therapy for curable oesophageal cancer patients. Anastomotic sites are prone to serious complications such as leakage, fistula, bleeding and stricture. Leakage of the anastomosis (AL) remains one of the main causes of postoperative morbidity and mortality. The purpose of this study was to identify predictors associated with postoperative leakage after Ivor Lewis oesophagectomy and its consequences in a single centre. We performed a retrospective analysis of 412 Ivor Lewis oesophageal resections in a single institute between 2005 and 2014. Univariable and multivariable logistic regression have been used to identify predictors of AL and its impact on postoperative outcome and overall survival. Kaplan-Meier curve was used to analyse overall survival and log-rank analysis to determine odds ratio. A total of 412 patients were evaluated. Mean age was 62 ± 11 years (77% male). Overall leak rate was 2.9%. In-hospital or 30-day mortality was 4.4%. Mean intensive care unit (ICU) stay was 1 day and mean hospital stay was 19 days. A history of renal failure, diabetes, higher American Society of Anaesthesiologists score and current cigarette and corticosteroid use were identified as predictors of AL on univariable analysis. Multivariable analysis identified active smoking [P = 0.05, odds ratio (OR) 4.34, 95% confidence interval (CI): 0.98-19.28] and active corticosteroid use (P < 0.001, OR 15.8, 95% CI: 3.25-76.7) as independent significant predictors. A history of diabetes tended to be associated with a higher leakage rate but failed to reach statistical significance. AL was associated with a longer ICU and hospital stay and a significantly higher mortality (42% in the AL group vs 3% in the control group, P < 0.0001). Anastomotic leakage after oesophagectomy is a major cause of postoperative morbidity and mortality. Identifying risk factors preoperatively can contribute to the prevention of postoperative complications.


Isolation of a Korean domestic microalga, Chlamydomonas reinhardtii KNUA021, and analysis of its biotechnological potential.
A freshwater microalga, Chlamydomonas reinhardtii KNUA021, was characterized for its potential as a biochemical feedstock. Its optimal growth was observed when the culture was incubated at 25°C and pH 9.4. However, the isolate was capable of survival and growth under a variety of temperatures (10-30°C) and pH (pH 4.0-12.0) conditions. The total lipid content of the isolate was 21.7% of dry weight and it was found that a high-value fatty alcohol, hexadecenol (C(20)H(40)O), was autotrophically produced by strain KNUA021. In addition, a nutritionally important C(18:3) ω3 (α-linolenic acid, ALA) was also identified in this photosynthetic microorganism as one of the major fatty acids. Hence, C. reinhardtii KNUA021 appears to show promise for use in the production of microalgae-based biochemicals.


Liver Transplantation in Recipients With a Positive Crossmatch: A Retrospective Single-Center Match-Pair Analysis.
A positive crossmatch (XM+) is considered a contraindication to solid abdominal organ transplantation except liver transplantation (LT). Conflicting reports exist regarding the effects of XM+ on post-transplant outcomes. The goal of this retrospective single-center analysis is to evaluate the influence of XM+ on relevant outcome parameters such as survival, graft rejection, biliary and arterial complications. Forty-nine adult patients undergoing LT with a XM+ between 2002 and 2017 were included. XM+ LT recipients were matched 1:2 with crossmatch negative (XM-) LT recipients based on the balance of risk (BAR) score. Patient and graft survival were compared using Kaplan-Meier survival analysis and the log-rank test. Comparative analysis of clinical outcomes in XM+ and XM- groups were conducted. Patient and graft survival were similar in XM+ and XM- patients. Rejection episodes did not differ either. Recipients with a strong XM+ were more likely to develop a PCR+ CMV infection. A XM+ was not associated with a higher incidence of biliary or arterial complications. Donor age, cold ischemia time, PCR+ CMV infection and a rejection episode were associated with the occurrence of ischemic type biliary lesions. A XM+ has no effects on patient and graft survival or other relevant outcome parameters following LT.


Quality assurance in eight adult medicine group practices.
Four evaluations of ambulatory medical care tasks were developed for use in quality assurance. The evaluations used medical records data and explicit criteria incorporating branching logic. They were implemented in eight general medicine provider groups in two teaching hospitals and six related health centers. Agreement with criteria among 316 provider responses to questionnaires varied from 57% to 100%. The percentage of cases with one or more variation from evaluation criteria, confirmed on peer review to have a deficiency in care, ranged by task from 6% to 42%, with substantial variation between sites. Physician reviewers from each site varied in leniency. Numbers of actions taken to correct deficiencies ranged by site and task from zero to six. Multisite evaluations revealed differences in performance and efforts to improve that are not apparent when each site conducts its own evaluations. More uniformly effective and impartial quality assurance is needed to correct some important deficiencies in care observed in this study.


A rapid method for staining inclusions of Chlamydia psittaci and Chlamydia trachomatis.
A new staining method was developed for the detection of inclusions of Chlamydia psittaci and Chlamydia trachomatis inclusions in cell cultures. Using a combination of methyl green and neutral red stains and washing at pH 5.0, inclusions were stained red while cell cytoplasm was pale pink and cell nuclei were pale green. The method was significantly better than Giemsa staining and comparable to immunofluorescence for detecting C psittaci inclusions. Its sensitivity for detection C trachomatis inclusions by dark field microscopy was similar to that of Giemsa staining.


Rapid synthesis and electrochemiluminescence behavior of CdTe nanoribbons.
A rapid chemical method has been developed for the synthesis of the CdTe nanoribbons with cubic crystalline phase. The method is based on the template-engaged synthesis in which the Te nanowires were used as template reagents. On the basis of a series of experiments and characterizations, the electrochemical property of CdTe nanoribbons was determined by the voltammetric technique. Furthermore, electrochemiluminescence property of CdTe nanoribbons was investigated. The results show that CdTe nanoribbons are helpful to obtain stable electrochemiluminescence emission for 1200 seconds.


Changes in systemic and pulmonary blood flow distribution in normal adult volunteers in response to posture and exercise: a phase contrast magnetic resonance imaging study.
Hemodynamics are usually evaluated in the supine position at rest. This is only a snapshot of an individual's daily activities. This study describes circulatory adaptation, as assessed by magnetic resonance imaging, to changes in position and exercise. Phase contrast magnetic resonance imaging of blood flow within systemic and pulmonary arteries and veins was performed in 24 healthy volunteers at rest in the prone and supine position and with bicycle exercise in the supine position. No change was seen in systemic blood flow when moving from prone to supine. Exercise resulted in an increased percentage of cardiac output towards the lower body. Changes in position resulted in a redistribution of blood flow within the left lung--supine positioning resulted in decreased blood flow to the left lower pulmonary vein. With exercise, both the right and left lower lobes received increased blood flow, while the upper lobes received less.


[Lymphocyte subpopulations determined by flow cytometry in chronic type B lymphatic leukemia].
For examination of surface characteristics of lymphocytes automatic analyzers of flow cytometry are used which make it possible to assess labelling with 2-3 monoclonal antibodies on one examined cell and provide thus more accurate data on the immunophenotype of proliferating cells. The objective of the present work was-using the method of flow cytometry and monoclonal antibodies-to detect surface signs on lymphocytes in the peripheral blood stream of patients with lymphatic leukaemia. In 29 patients with chronic lymphatic leukaemia type B (B-CLL) CD signs were examined, using flow cytometry and the findings were compared with those obtained in a control group of 63 healthy subjects. Evidence of CD 19+ CD5+ lymphocytes (B1 cells) in B-CLL (83.4 +/- 15% vs. 3.5 +/- 1.9% in controls) was of diagnostic importance. These CD5+ B cells are polyreactive, "memory B" lymphocytes which contrary to "conventional" lymphocytes B2 (CD5-B) do not differentiate further to plasma cells. Accumulation of B1 (CD5+ B) lymphocytes was, on the other hand, associated in patients with B-CLL with a decrease of B2 (CD5-B) lymphocytes (2.8 +/- 4.0% vs 9.0 +/- 4.2%) (p < 0.01). This finding can in case of excess of B1 (CD5+ B) lymphocytes explain the tendency of patients with B-CLL to develop autoimmune complications (e.g. AIHA); and conversely a decrease of B2 (CD5-B) lymphocytes can lead to hypogammaglobulinaemia which is also associated with B-CLL. A tendency towards autoimmunity may be also promoted by a decline of so-called inductors of suppressor cells (CD 4+ CD45RA); in patients with B-CLL among CD4 T lymphocytes 32.5 +/- 15% CD 45RA+ cells were found, as compared to 43.0 +/- 14.8% in controls (p < 0.011) and a lower ratio of true suppressor T cells (CD8+ CD11b+) in patients with B-CLL: 47.0 +/- 17.6% CD11b+ from CD8+ cells, as compared with controls 80.4 +/- 13.3 CD11b from CD 8+ cells (p < 0.01). The method of flow cytometry with double fluorescence thus contributes to the accurate diagnosis of B-CLL, to monitoring of the therapeutic effect but also to knowledge of the immunopathology of the disease.


Natural infection of Delta mutant of SARS-CoV-2 in Asiatic lions of India.
The current pandemic caused by a novel coronavirus (SARS-CoV-2) has underlined the importance of emerging diseases of zoonotic importance. Along with human beings, several species of wild and pet animals have been demonstrated to be infected by SARS-CoV-2, both naturally and experimentally. In addition, with constant emergence of new variants, the species susceptibility might further change which warrants intensified screening efforts. India is a vast and second most populated country, with a habitat of a very diverse range of animal species. In this study we place on record of SARS-CoV-2 infections in three captive Asiatic lions. Detailed genomic characterization revealed involvement of Delta mutant (Pango lineage B.1.617.2) of SARS-CoV-2 at two different locations. Interestingly, no other feline species enclosed in the zoo/park were found infected. The epidemiological and molecular analysis will contribute to the understanding of the emerging mutants of SARS-CoV-2 in wild and domestic animals.


Controlled Tuning of the Size of Ag-Hydrosol Nanoparticles by Nonstabilized THF and Detection of Peroxides in THF.
Surface plasmon extinction (SPE) spectra of plasmonic nanoparticles (NPs) are sensitive indicators of their composition, size, shape, interparticle interactions, and of the dielectric constant of their ambient. In this study, rapid changes in SPE spectra of Ag NPs suggesting variations in NP size and concentration were detected after addition of aged tetrahydrofuran (THF). Using time-dependent UV/vis spectroscopy combined with factor analysis, transmission electron microscopy imaging, selected-area electron diffraction, and energy-dispersive X-ray analysis, we observed that an over-limit amount of aged THF fully dissolved Ag NPs with no plasmon recovery. By contrast, an under-limit amount led to incomplete dissolution of Ag NPs and, after reaching the turnover point, to spontaneous recrystallization on residual Ag nuclei, as demonstrated by the SPE band intensity recovery to the original or even higher values. The newly formed Ag NPs were isometric, and their diameter was dependent on the added amount of THF. Furthermore, both Ag NP dissolution and recrystallization were caused by THF peroxides and their reduction products. Therefore, the dissolution of Ag NPs and the resulting hydrosol bleaching may be used as an indicator of the presence of peroxides in THF. Moreover, the reaction of aged THF with Ag NPs can be employed as a tool for tuning the size of Ag NPs in hydrosols.


Childhood adversities and psychosocial disorders.
Adverse childhood experiences--especially inadequacies in early parental care--are associated with elevated rates of both acute and chronic psychosocial disorders in adult life. In most instances, adverse outcomes are confined to a minority of children exposed; variations in the severity or pervasiveness of early risk, individual differences in susceptibility, and interactions with later stressors are all thus likely to be important in mediating effects. At present, knowledge of intervening processes is limited, and dependent on retrospective studies of adult samples or short-term longitudinal findings in childhood. We review current evidence on the long-term outcomes of prenatal divorce, childhood maltreatment, and institutional rearing, and on the early antecedents of depression and antisocial behaviour in adult life, to highlight possible interviewing mechanisms. Most long-term sequelae seem likely to depend on a series of shorter-term links, some running through elevated risks of continued environmental adversity, others through psychological vulnerabilities and problems in social relationships.


Dextran T fractions substituted with cibacron blue F3G-A as carriers for mouse interferon.
Commercial dextran T fractions covering the molecular weight (Mt) range 10,000-2,000,000 were substituted with a covalently linked chromophore: Cibacron blue F3G-A. Mouse interferon (IF) was found to bind firmly to the blue dextran (BD) fractions. Fractions of high Mt (BD 2000 and BD 500) associated with IF are precipitated from the solution by polyethylene glycol (PEG). Fractions of lower Mt (BD 70, BD 40 and BD 10) associated with IF are only partially, if at all, precipitated by PEG. However, when BD-IF complexes of various Mt were analyzed by chromatography on Sephadex G-150, IF activity migrates together with BD and not at the distance characteristic of native IF. These data suggested that IF is bound to various BD fractions. BD-IF complexes of various Mt have almost the same antiviral and anticellular activities as native IF. BD-IF complexes are neutralized to a greater extent by antibody than native IF. Clearance of BD 70-IF complex from the mouse peritoneal cavity is slightly slower than native IF. However, the i.v. clearance of both forms of IF is almost the same.


Sulfamides and sulfamide polymers directly from sulfur dioxide.
SO2 gas is effectively used for the preparation of N,N'-diarylsulfamides and shape-persistent sulfamide polymers, which utilize a network of intermolecular N-H...O=S hydrogen bonds to self-assemble into soft porous materials.


Influence of membrane phospholipid composition and structural organization on spontaneous lipid transfer between membranes.
Investigations were carried out on the influence of phospholipid composition of model membranes on the processes of spontaneous lipid transfer between membranes. Acceptor vesicles were prepared from phospholipids extracted from plasma membranes of control and ras-transformed fibroblasts. Acceptor model membranes with manipulated levels of phosphatidylethanolamine (PE), sphingomyelin and phosphatidic acid were also used in the studies. Donor vesicles were prepared of phosphatidylcholine (PC) and contained two fluorescent lipid analogues, NBD-PC and N-Rh-PE, at a self-quenching concentration. Lipid transfer rate was assessed by measuring the increase of fluorescence in acceptor membranes due to transfer of fluorescent lipid analogues from quenched donor to unquenched acceptor vesicles. The results showed that spontaneous NBD-PC transfer increased upon fluidization of acceptor vesicles. In addition, elevation of PE concentration in model membranes was also accompanied by an increase of lipid transfer to all series of acceptor vesicles. The results are discussed with respect to the role of lipid composition and structural order of cellular plasma membranes in the processes of spontaneous lipid exchange between membrane bilayers.


Improvements in Immune Function and Activation with 48-Week Darunavir/Ritonavir-Based Therapy: GRACE Substudy.
Objective. During the course of HIV infection, progressive immune deficiency occurs. The aim of this prospective substudy was to evaluate the recovery of functional immunity in a subset of patients from the GRACE (Gender, Race, And Clinical Experience) study treated with a DRV/r-based regimen. Methods. The recovery of functional immunity with a darunavir/ritonavir-based regimen was assessed in a subset of treatment-experienced, HIV-1 infected patients from the GRACE study. Results. 19/32 patients (59%) enrolled in the substudy were virologically suppressed (<50 copies/mL). In these patients, median (range) CD4+ cell count increased from 222 (2, 398) cells/mm(3) at baseline to 398 (119, 812) cells/mm(3) at Week 48. CD8+% decreased significantly from baseline to Week 48 (P = .03). Proliferation of CD4+ lymphocytes in response to CD3+/CD28+, phytohemagglutinin, and pokeweed was significantly increased (P < .01) by Week 12. Proliferation in response to Candida and tetanus was significantly increased by Week 48 (P < .01 and P = .014, resp.). Staphylococcal enterotoxin B-stimulated tumor necrosis factor-alpha and interleukin-2 in CD4+ cells was significantly increased by Week 12 (P = .046) and Week 48 (P < .01), respectively. Conclusions. Darunavir/ritonavir-based therapy demonstrated improvements in CD4+ cell recovery and association with progressive functional immune recovery over 48 weeks. This trial is registered with NCT00381303.


The Clinicopathological Significance of Basal Markers in Early-Stage Invasive Carcinoma of No Special Type of the Breast.
Basal markers [cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR)] are used in identifying the basal-like breast carcinoma subtype, which is associated with a poor prognosis. However, the clinicopathological significance in early-stage invasive carcinoma of no special type (IC, NST) has not been well established. In a five-year period, 133 female patients with early-stage IC, NST with a median follow-up time of 89 months were included. The immunohistochemistry-based molecular subtypes were identified according to ASCO/CAP guidelines in 2013. The cutoff values for basal positivity were determined as 10% for each marker. Basal positivity was recorded in 83.3% (5/6) of triple-negative breast cancers, 50% (2/4) of HER2-enriched, 18.6% (13/70) of luminal B, and 8.3% of luminal A (4/48) subtype. CK5/6 and EGFR positivity were significantly associated with ER negativity (p < 0.001). EGFR positive cases were significantly associated with PR negativity and HER2 positivity compared to negative cases. However, basal positivity was not associated with the patient outcome (p = 0.006 and p = 0.004, respectively). Basal positive IC, NSTs were associated with hormone receptor negativity and HER2 overexpression; these patients would therefore be less likely to respond to hormonotherapy and more likely to benefit from anti-HER2 treatment as well as dual-kinase inhibitors. The lack of standardization of the definition of basal marker positivity may contribute to the conflicting results of prognostic studies. Hence, further studies focusing on developing a standard protocol for determining basal marker positivity are needed not only for IC, NST but also for other histological types of breast cancer.


Microphotometric analysis of protein-bound thiols and disulfides with an azogenic maleimide.
The chromogenic thiol reagent N-(4-aminophenyl)-maleimide (APM) was used to provide a sensitive procedure for the determination of protein-bound thiol group, both before and after reduction of disulfide bonds by tri-n-butylphosphine. The bound reagent is diazotized and coupled at low pH to N-(1-naphthyl)ethylenediamine to form an intense magenta label (lambda max 547 nm) with a high molar absorbancy (epsilon 547 = 49,800 cm2/mmol). The validity of absolute quantitation afforded by the method was shown by comparing the results with standard chemical analyses of thiol contents in a model system. Furthermore, the applicability of the procedure to biological objects was shown on isolated epididymal bull sperm heads.


A morphological analysis of an in vitro model of cytotoxic antitumor activity.
Models of adoptive immunotherapy and cytotoxicity of lymphocytes isolated from tumor tissues were studied. A microcytotoxicity model utilizing serum-free culture conditions was evaluated by light microscopy, scanning electron microscopy, and transmission electron microscopy for antitumor activity. By examining morphologically the relationship between peripheral blood mononuclear cells and tumor-infiltrating lymphocytes, it was demonstrated that the latter and macrophages had morphological features similar to the cytotoxic cells obtained in vitro from peripheral blood. When allowed sufficient time in our culture conditions, the tumor-infiltrating cytotoxic cells seem to kill the tumor cells within a few days to many months. The ultrastructural morphology of the interaction between the cytotoxic cells and the tumor cells was described as well as some proteinaceous secretory granules that seem to be transferred to the tumor cells through these interactions.


Modular pyridine synthesis from oximes and enals through synergistic copper/iminium catalysis.
We describe here a [3+3]-type condensation reaction of O-acetyl ketoximes and α,β-unsaturated aldehydes that is synergistically catalyzed by a copper(I) salt and a secondary ammonium salt (or amine). This redox-neutral reaction allows modular synthesis of a variety of substituted pyridines under mild conditions with tolerance of a broad range of functional groups. The reaction is driven by a merger of iminium catalysis and redox activity of the copper catalyst, which would initially reduce the oxime N-O bond to generate a nucleophilic copper(II) enamide and later oxidize a dihydropyridine intermediate to the pyridine product.


Multiple benign adnexal tumours: Anything but benign.
Muir Torre syndrome is an autosomal dominant disorder characterised by germline mutations in mismatch repair genes involved in DNA repair, leading to microsatellite instability and a propensity to tumour formation. We report a case of a 67-year-old gentleman who underwent biopsy of a smooth nodular lesion on the nasal tip, histopathologically consistent with sebaceous adenoma. Immunohistochemistry suggested a loss of MSH6. Subsequent colonoscopy identified a poorly differentiated adenocarcinoma, with loss of staining for MSH6 and a germline mutation identified on genetic analysis. These findings were consistent with a diagnosis of Muir Torre syndrome. Whilst there is controversy in the literature regarding universal screening for Muir Torre syndrome, the early detection of visceral neoplasms is crucial. The authors strongly support screening for Muir Torre syndrome (with patient consent) upon discovery of a cutaneous sebaceous neoplasm, even in the absence of a personal or family history of visceral malignancy.